Good evening ladies and gentlemen. Thank you for standing by and welcome to the Agenus Annual Meeting of Stockholders twenty nineteen. At this time all participants will be in listen only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by 0. After today's presentation, there will be an opportunity to ask questions.
To ask a question, you may press star then 1 on your touch tone phone. To withdraw your question, please press star then 2. Please note this event is being recorded. I would now like to turn the conference over to Doctor. Garo Armen, Chairman and CEO of Agenus.
Doctor. Armen, please go ahead.
Thank you very much. We will have a unique format for today's shareholder meeting. We will start with the formal portion, followed by a brief update and a talk show format with a special guest that we have, including Q and A that will arise from both the panel as well as the members of the audience. To start, good afternoon, everybody, I'd like to call to order the formal portion of the Agenus Annual Meeting of Stockholders. Among participants in the meeting today are members of our Board of Directors, Brian Corvese, Bill Jordan, Ulf Windberg, and Tim Wright.
I'd like to thank them and our Agenus team and each one of you for your time and commitment to Agenus. Now I'd like to introduce you to Evan Kerns, the company's Vice President and General Counsel. After the completion of the formal portion of the meeting, I'll come back and give you an update on the company's progress and future plans. Evan, please take the podium.
Thank you, Gail. This meeting was called by the Board of Directors of Agenus on April 1039. I have received an affidavit of distribution from Broadridge Financial Solutions. That notice of this meeting was furnished by the company on or about April 2639 to every holder of record of common stock as of April 2439, the record date for this meeting. The Board of Directors has appointed Christine Klaskin as the Inspector of Elections for this meeting.
Ms. Klaskin has signed the oath of office which will be filed with the minutes of the meeting and she has prepared a report stating that the holders of a majority of the outstanding shares of common stock as of the record date are present in person or are represented by proxy at this meeting. Therefore, I declare that a quorum is present. We are now ready to proceed with the business of the meeting. Let me briefly describe the voting procedures.
We will vote by proxy and by written ballot. If you have previously voted by proxy, you do not need to complete a ballot. Your vote will be counted. If you're eligible to vote and have not submitted your proxy or if you want to change your vote, please raise your hand now and the Inspector of Elections will distribute you a blank ballot. Is there anybody that needs a ballot that doesn't have one?
Excellent. It is now two minutes after five on June 1939, and the polls for each matter to be voted on at this annual meeting are now open. Proposal number one, the first item on the agenda is to elect Brian Corvese and Tim Wright as class one directors, each for a term of three years expiring at the twenty twenty two annual meeting. Their qualifications are described on pages seven through eight of the proxy statement, The Board of Directors unanimously recommend that stockholders vote in favor of them vote. Anybody voting by ballot, please mark your ballot for proposal number one now.
Proposal number two, the second item in the agenda is proposal to approve an amendment to our certificate of incorporation to increase the number of shares of common stock authorized for issuance from $240,000,000 to 400,000,000 shares. A detailed description of the proposal can be found on pages 35 to 36 of the proxy statement and the board unanimously recommends that shareholders vote in favor of this proposal. Anyone voting by ballot, please mark your ballot now. The third item on the agenda is a proposal to approve the company's 2019 equity incentive plan. A detailed description of the proposal can be found on pages 37 through 45 of the proxy statement, and the board unanimously recommends that stockholders vote in favor of this proposal as well.
Anyone voting by ballot, please mark your ballots now. Proposal four. The last item on the agenda is a proposal to ratify the appointment of KPMG as the company's independent registered public accounting firm for the fiscal year ending December 3139. A detailed description of the proposal can be found on Pages 46 to 47 of the proxy statement, and the board unanimously recommends that shareholders vote in favor of this proposal. Please mark your ballots now.
We will now collect any ballots in the audience. Please raise your hand and Ms. Klaskin will collect and record them. The Inspector of Elections will not accept ballots, proxies or votes or any changes or revocations submitted after the closing of the polls. It is now 05:05 on June 1939 and the polls the matters to be voted on at this annual meeting are now closed.
Inspector of Elections, please prepare your report on the results of the voting. Thank you. Inspector of Elections has certified that each of the proposals placed before the meeting have been adopted by the requisite votes. I hereby declare that each of the proposals presented at the meeting have been approved by the shareholders. That now concludes the formal portion of the meeting.
Before I turn things back to Garo, I would like to note that the remainder of this meeting will include forward looking statements, including statements regarding clinical development, regulatory plans and timelines. These statements are subject to risks and uncertainties. We refer you to our SEC filings for more details on these risks. Carol?
Thank you very much, Evan. Before I start, I should indicate that once again, all remarks contain forward looking statements that are subject to risks as Evan said, and we refer you to our full filings. Today, we are adapting a format intended to take our communications to a new level. To help with this, we have asked John Nasta to participate in the proceedings. John, who I am sure many of you are familiar with, is a deep thinker in the world of science, medicine, and innovation.
He's a provocateur who challenges the norm. Is a member of the Google Health Advisory Board, he pens the top global blog and health and technology for Forbes Magazine, and is the founder of NastaLab, an innovation think tank. He is internationally recognized as a thought leader in the future of health innovation. Before I invite John, I will provide you with a report and exciting updates on Agenus. We are entering an unprecedented period where innovation and speed will drive future success in our industry like never before.
There's no ambiguity about this. Obsolescence rates are already increasing. We believe innovation and speed will drive success in our field immuno oncology as we have seen in the field of technology. We have invited John to introduce you to the Agenus of today in the context of the broader world of business, health, and technology. In the past three years, we have discovered and are developing a broad pipeline of highly innovative immuno oncology products that we believe represent the next generation innovations in treating patients with cancer.
This year marks our twenty fifth anniversary represented by persistence and innovation in turning the body's immune system into a weapon to fight cancer. Some of you may remember we were the first company to pioneer individualized treatments for patients with cancer at a time when the world of individualized word, the word individualized, was frowned upon. We were pioneers in the immunology of cancer when establishment was convinced cancer could not be conquered immunologically. Now, whether in the form of cell therapy or checkpoint antibodies, these treatments are called immune oncology. They represent the most promising approach for cancer patients, with a number of these patients being cured of their previously incurable cancers.
We at Agenus are the major inflection point. We have built a pipeline that is as broad as it is deep. It is comprised of our CTLA-four and PD-one antibodies, but we have not stopped there. Our innovative teams have discovered, and we are currently developing second and third generation immuno oncology molecules beyond the first generation CTLA-four and PD-one antibodies. Our pivotal trials are growing than we had indicated before.
And we expect that we will file earlier for our BLA than we had indicated in our earlier reports. The importance of having first generation CTLA-four and PD-one antibodies under our roof is that they give us the flexibility to design high impact combinations without the price or access restrictions if one were to be dependent on these products from third parties. Our plan is to register and launch these products in The U. S. And seek partners for commercialization outside of The U.
S. We are expanding our efforts with our second and third generation molecules that are now in the clinic. Amongst them is a very exciting molecule, our second generation CTLA-four, codenamed AGEN1181. We believe this molecule has the potential to expand the commercial potential of our PD-one very substantially. AGEN1181 is currently in the clinic, and we anticipate clinical readouts by end of this year.
We also plan to start combinations of our next gen CTLA-four with our own PD-one molecule very soon. This agent, with enhanced features, could benefit patients who currently respond to first generation CTLA-four, but more importantly, expand the patient population to those who don't respond to first generation CTLA-four antibody. And this, by the way, non responsiveness is due to a genetic polymorphism, who you may hear from one of our lead scientists, Don Chan, later on. Clinical data from our second generation CTLA-four could represent an important value inflection point for us. In defining our own U.
S. Commercial opportunity and by enabling our ability to monetize on ex U. S. Rights to further accelerate the development of our own broad pipeline. I might also add at this point that our discussions with third parties about various licensing and partnership activities are at an all time high, and that is due to the performance of the molecules that we have gotten to this advanced stage of research and development.
Our next generation pipeline is clearly the focus of our company. And this focus is to achieve high and durable responses. This means shorter trials, lower trial costs, and more rapid product registration. Our opportunities for combinations include combinations with our own checkpoint antibodies and bispecific. Our cell therapies, including our allogeneic cell therapy, expected to enter the clinic in the next six to nine months.
Our access to our broad portfolio of agents is a major advantage for us, which helps our ability to rapidly deliver on our high impact strategy, including our strategy with combinations. Agenus is a rare breed with four different therapeutic modalities comprising checkpoint antibodies, cell therapy, neoantigen vaccines, and adjuvants. Our discoveries are designed to have high impact in the treatment of patients with cancer. We are positioned to deliver these high impact combinations with full control of the key components of our portfolio, and very importantly, full control of total cost and each component cost, which is almost unprecedented in the industry. Our fully integrated capabilities, which include from discovery all the way to all the CMC functions and manufacturing, have delivered concept to IND in less than twenty four months.
Our record of operational execution in getting new discoveries to the clinic in the past three years speaks for itself. 11 INDs in three years, and it hasn't stopped. Our agility and flexibility position us to deliver products that can move to the market faster to benefit all of our stakeholders and patients. Our objectives are to emphasize high impact therapies with small shorter trials, as I mentioned before, that deliver meaningful benefit and rapid regulatory and commercial success. With this, we endeavor to transform what a diagnosis of cancer means to patients today.
And I will conclude my formal remarks, and now we will turn the meeting to a more informal format with the infamous John Nasta taking the podium, followed by a Q and A session. John?
Thank you, Jerome. I think I have to turn my microphone on for everybody. Good evening or good afternoon. Do you ever feel that you're at the center of New York, the epicenter of where things are happening? I want to try to explain my perspective on the world today and how Agenus uniquely sits into that dynamic.
And I think that the net takeaway, at least from my perspective, is to recognize that we are truly lucky to be alive today. We are at, and I'm going to steal your word, Garo. We are at an inflection point. And I want to talk about that a little bit. We are at a fundamental change in humanity.
And those changes are reflected very, very nicely in what agenus is doing in the science, creating a fundamental shift in the way we live and the way we treat diseases and particularly the way we manage and treat cancer. But I want to go back a little bit because we're moving forward at such a tremendous speed that it's almost unrecognizable. It's easy to say that we are at an inflection point in human history to use words like that. They're just we might as well throw in things like big data and artificial intelligence. They become almost meaningless.
And my challenge is to bring meaning to today's inflection point. So I wanna go back. Let's go back about a hundred years and look at similar changes that transformed humanity. Now if you think back, if you look through your history books of your imagination, you wonder what happened a hundred years ago. What happened in the year 1900?
And the reality is that very little happened in the year 1900. One could argue that metaphorically I could say nothing happened in the year 1900. But things started to take shape around 1915, 1914, 1919. We saw things like the discovery of the mass of an electron or the charge of an electron. But we also saw things like women's suffrage, women's right to vote, World War one, the Russian Revolution.
The century began at that time, And we saw interesting elements in that century around strife. It was a very, very difficult time to be alive. Yet there was the emergence of technology and science that yielded a sense of wonder. And that wonder also created the sense of engagement that this is my century, that this is the time where things are changing. And we can compare that to what's going on today in the world.
I'll ask everyone in the room, what happened in the year February? It's the same answer, right? Nothing? Probably nothing. Interestingly, one could argue that maybe in the year February, Y2K didn't happen.
But it was a nonevent. It took us to 2007 to have something really interesting happen, and that was the emergence of the smartphone. But what we're seeing today in 2019 is a convergence of the same social, technological, humanistic forces in the world today. Certainly there is a high level of strife whether that be social or political. Add to that the layer of health, that the emergence of cancer, of obesity, of metabolic syndrome, of central nervous system disorders.
It's a critical time in human history quite different than five or ten years ago, certainly from the year February. But the promise of technology is moving us in a new direction. And similar to a hundred years ago, that point of change is happening now uniquely. And with it comes that sense of wonder, that sense of transformation, that sense of enthusiasm and power. It's been said that the six most powerful words in human language are, I love you.
And you know what the other three are? You have cancer. Extraordinary emotional, physical constructs that are associated not only with death and dying, but even financial ruin. We are at, in essence, a precipice from certain perspectives. But we're seeing now this transition, that sense of wonder and that sense of empowerment.
And who sits in the center of that dynamic today? And that's why we have the A here, because the A is in essence the beginning of the alphabet. It's beginning of the journey. The more I learn about Agenus and Garo and the innovations I find out that fundamental insights into the early days of treating cancer in a new way, the early foundations of immunotherapy, happen in the construct of this room, of this mind share. And I think that's very, very important, sitting at the A.
But I don't want to talk about the A because that's the known quantity. I want to talk about what the A is in the world of this thing called exponential change and this thing called the inflection point. And that really searches around the value of X. And we can talk about X in the context of many interesting things. We can talk about it as the unknown, as the variable, as what we're looking for.
Because in today's world it's not only about what we're looking for, but it's the context in which we are living and looking for. So I apologize for the calculus analogies, but I thought it was kind of appropriate. Because in today's world, the search for X, the search for cure, the search for insights has to be considered in the context of this thing. And it's DX DT. And that's the change with respect to time.
From a simple perspective, it's speed. We live in a world where speed and data are extraordinary components that define our lives. Think about this. It took sixty seven years for the airplane industry to reach 50,000,000 people. Sixty seven years.
By the way, the airplane came about around 1916, 1917, again that same time a hundred years ago that we're seeing today. It took Facebook three years, three years to reach 50,000,000 people. What about Pokemon GO? Anybody want to guess? 50,000,000 people in nineteen days.
Nineteen days. That's the world that we live in. That's the change in X over the change in time. That's where we live. We live in this profound dynamic defined by exponential change.
The rate of change is extraordinary. And I think it's very important to recognize that Agenus sits at that scientific and human inflection point. And here's what it looks like sort of graphically, if you will. You are here. You are at this inflection point in the human experience that's going to change the game.
And it's an interesting kind of dynamic to look at exponential change because it's a little tricky. We define it by exponential, but there are a few other words that come to mind when we talk about this nature of change. And the first one is that change is becoming democratized. In the old days of clinical medicine, we would go to the doctor and he would give us a pill and we'd go home and we'd get on with our lives. It might work, it might not work.
But it was he who gave us a pill. We lived in the domain of control. And control is changing to collaboration. The collaborative experience of scientists, of researchers, of doctors, patients that are changing the game. The democratization of the world that we live in is extraordinarily important.
It's been said that the new competitive advantage is collaboration. So perhaps we live in a bit of a collective collaboratory that defines the nature of change. But beyond that, there's another element to this, and that's disruption. Ray Kurzweil, a great futurist, talked about disruption in the context of ripping at the fabric of humanity. Ripping at the fabric of humanity.
That's the nature of the change that we sit in. The nature of the change that's being facilitated by the innovations in scientific thinking that's going on here today. So disruptive change is extraordinary. We have to change the way we think about the aspects of science and medicine, particularly in oncology. Now the interesting thing is that this curve that we talk about, this exponential curve, is a little tricky because we generally live in the good old fashioned world of linear growth, whether it be a business plan, our IRA.
If we could track at 8% or 10% or 12% or 6% growth year after year after year, it's a good feeling. It's a comfortable feeling because we could predict. The interesting thing about exponential growth, and this is important because this is where Agenus sits. When we go back and talk about you are here, I talk about you individually, but also as a company at this unique point where innovations are about to click and change. So take a look at this curve.
This is the juxtaposition between exponential change and linear growth. Linear is comforting. We can predict very, very easily by simple extrapolation that I know 5% or 10% growth, whatever it may be. But the interesting part of this curve here is that when you look at early stage development in an innovative model, in a model that takes chances, in a model that takes risks, in a model that will actually tear at the fabric of scientific thinking and change, it starts off in a problematic place. What's happening here?
The early part of the growth of an exponential dynamic, a game changing dynamic is below good old fashioned linear growth. So good old fashioned thinking, good old fashioned perspectives on business, on finance. But look at this model sometimes and not be too pleased. That's the interesting thing about exponential change. That's why we're sitting at this spot where we move beyond the linear curve.
And to me this defines what Agenus is doing. Not because of a simple molecule, not because of a simple platform, but because of a convergence of events that are allowing for the ability to look at and treat cancer in a new and extraordinary way. Once the inflection happens, you move into a new dynamic where we're above linear change. This is the spot where change becomes disruptive, but change becomes profound. Change becomes, dare I say, curative.
Change becomes the game changer, if you will, that allows new insights to drive new therapies. This is where you live. I want to make this very, very clear. This is the promise of the platform of the research of the thinking at Agenus. I've studied this very carefully.
And when you look at this point of inflection, it's really where you live beyond that. So when I drive up to Boston, I feel like I'm coming to this epicenter of brilliance. There are so many smart people I get a headache when I drive up here. But it's important to recognize that that is the pain of disruption. That is the excitement of disruption.
And as we move through this inflection point and I think that it's today. It's not the year February. It's really something that's happening now. And I think that's the magic of clinical science. And that's where Agenus sits very uniquely at that inflection point in human history.
And I think we're going to talk a little bit about that more in-depth. So thank you very much. And I want to kind of tease this apart a little bit and understand this. So for a guy who doesn't know science, I want to understand this convergence of methodologies and technologies. Because I've heard that time and time again that it's not a compound, it's not a PDE1, but it's a cluster advantage that come together in an EU way.
Help me understand that a little bit, Dara.
Well, John, first of all, I wouldn't characterize your knowledge as not being scientific. You're way up in terms of your sophistication and brilliance. To your point, you know, in our field, perhaps in America, we're very short term oriented. Mhmm. And one clear fact about us as a company, as a team of people, is that perhaps we were way, way too early for our time when we declared immunology would potentially cure cancer.
And it's taken a long time and it's required a lot of patience and staying power. And if you do a Harvard case study of our company and go back to the beginning and sort of extrapolate all the facts and track that we have followed, you would have predicted that we wouldn't be around and yet we have persisted. And very importantly in the last three, three and a half years, we've delivered unprecedented discoveries to the clinic. Unprecedented. I mean, as I said earlier, 11 INDs in three years span far exceed anybody else's IO efforts in the industry.
Hold
that thought, because I want to there's a concept that I've been thinking about that's called disrupting the disruptor. And what I mean by that is that the speed, the clinical speed, the experimental speed that you can move at not only solves clinical dilemmas, but it allows you to get to market faster. Because in today's world, if it takes two, three, four, five years to develop a compound, you very well may be trumped by other innovators who can work more agilely or more quickly. So I think that's a very unique advantage that I've learned.
I mean, in our industry, as you know, this is a very important point, as you said, John. In our industry, it's not just about innovation, but it's also about hurdles getting in the way of that innovation getting to the finish line as expeditiously as possible. And those hurdles include regulatory hurdles, and I'm not, this is not to blame the regulatory agency, it's just that there is a regulatory body that sits, that dictates what you can do, what you cannot do, and that's something that doesn't exist in technology, for example. Technology industry has no such hurdle. It's strictly driven by innovation.
So balancing between your innovation and regulatory hurdles is one issue. Balancing between one's dependence on third parties is another issue. For example, if I have to depend on third parties to manufacture product, to develop cell lines, for combinations, for example, I'd be behind the curve continuously. And so we have put into place a deliberate strategy over the last three and a half, four years to bypass these things, and we are unique in that regard. We have all of these capabilities in house so that that set of hurdle is not a hurdle for us.
On the regulatory side, because we are at a very important inflection point of much more effective products coming to the clinic, that hurdle organically is starting to disappear. So that's why when you talk about your inflection point, that exponential change, it's driven by those factors, but of course you have to be a player. Without being a player, you cannot take advantage of that inflection point, and that being a player is a function of a lot of the brilliant minds that are in this room, including the young man next to me and the lady next to him, who have pulled all of these efforts together. And of course, thanks to every member of our team and our board who has been fantastically supportive of it throughout, and our shareholders.
Pharma's elusive search for identity has become a biopharmaceutical company because they want to share the heritage of biotechnology now. I wonder if you're if it's fair to say that you're an exponential biotech company. Maybe there's something about the speed and the ability to pull together ideas and thinking and move them along in a way that's consistent with what the market demands today. You know?
I think, I mean, I'll ask some of the consumers and drivers of this very process. Dan and Jen and perhaps other members of the team can participate. But Dan, why don't you go first?
You're right. I
think you talked about inflection points Mhmm. In our company, but we must recognize that for the first time in the history of our company, we have all the necessary tools, technologies, and capabilities to address every major cancer out there. And when people ask about what's unique, speed, yes. Innovation, absolutely. But it's our pipeline, The way this is designed, the way we can bring it together to advance novel therapies for patients is how Agenus is going to win the race.
Keep going on that because I want to tease that out a little bit. Because you talk about novel therapies. That's sort of in quotes. Is it novel therapies to build a combination protocol? I mean, what's the I want to tease this out a little because I think it's important for the people who are listening to recognize that this is a point of discovery that is rich in science.
Let us recognize one thing.
Any patient who has beaten cancer, regardless of what therapy they receive, response is what underscored their ability to beat cancer regardless what Mhmm. They're We recognize that. We recognize that immunotherapy is the only therapy so far that has brought curative responses to patients. We were founded on the principle that cancer is a personalized disease, and we have built a pipeline to address that. And we have recognized that the immune response to cancer is equally complex.
So our ability to therapeutically modulate each and every node is empowering because then you can bring curative combinations. I'm going to stop you.
I'm going stop you right there because each and every node. Okay. So I'm sure there are people who recognize what that means, but most people don't. And as I've studied, Agenus, very deeply, what I found unique is when you refer to those nodes, and I want you to kind of confirm this or just smack me down, but those are sort of immunological stages of cancer. Is that when you talk about nodes Absolutely.
So keep in mind that a patient's response is gonna be different from indication to indication from patient to patient. And we have the ability to address that. We have the ability to unblock what's preventing their immune system and as well support that immune system.
What if I can't exists in the context of mainstream IO or even the broad construct of oncology.
I would say that, you know, we are at the leading edge of uncovering novel therapies and advancing novel therapies. I I don't consider what we do as mainstream. We were never mainstream. We were So we were the first to recognize cancers personalized. We were the first industrialized cancer vaccines, And we have put novel products into the clinic.
Our clinical data supports it. So I'm a clinician who's going to gravitate to the ubiquitous PD-one molecule as the panacea for cancer, as the go to IO therapy, right? But the reality is that that's a false premise because you have to understand the state of the immune system, the fatigue state of the T cell. I know I shouldn't have said that because I'm in way over my head. But to me, recognizing that to align therapies with the nodes or the immunological status of the patient is one of the big game changers.
Is that making sense?
It absolutely makes sense. And let's consider this, you know, when we consider when immunotherapy got famous with CTLA-four, that made immunotherapy famous, ipilimumab. A lot of people moved away from CTLA-four and went to PD-one. Right? Right?
Why? Because they didn't understand CTLA-four at the time. It was toxic. We wanted a safer method to enhance the immune system. Today, we have recognized the importance of both anti PD-one and anti CTLA-four therapies, and Agenus is uniquely positioned
So I'm going to back up now. So what I'm hearing is that the emergence of new immuno oncology therapies as well as the ability to stage or gauge immunological status is important. But combination therapy seems to be a critical element of therapy. Absolutely.
There's no silver bullet to cure cancer.
But you guys have something unique, and I hear this in the back of my head as mic reverbs a little bit. Hear this in the back of my head that the ability to develop and create combination therapy within your own IP, your own domain, is a very powerful advantage. And I don't think the market I don't understand it. But I don't think the market understands how unique that is, not only as a therapeutic model to advance rapid innovation, but also as a proprietary business model so that you don't live under the hegemony of these other pharma companies that control these compounds.
I think, Jen, maybe you can elaborate on this because you're right in the midst of coordinating all of these efforts with combinations accelerating in the clinic.
I'd be delighted to. And I think that just to go back to a couple of points that both you have made, John, and you as well, Dan, the idea of the combinations, why are they important? And we are at the bleeding edge of this because we know that tumors, in order to be combated by the immune system, we have to address a couple of features. First, the immune system has to know that cancer is there. So we have the approaches that allow the immune system or exposes the tumor to the immune system, like a vaccination approach.
And in that case, if the immune system doesn't know the tumor's there, PD-one will not work. This doesn't work. So you need the vaccines. You need other therapies or some approaches that we have that we haven't yet disclosed in order to expose a tumor. At that point
Let me hold on right there. Yes. Okay? Explain to me this vaccine word, because I think a lot of people who are listening misinterpret a vaccine like chickenpox or one of these others. So when do you mean vaccine, in a sentence or two?
So our immune system was designed effectively to protect us about diseases coming in, right? It's physically designed that way. It's immunologically designed that way. When you take something that's inside of you and you expose it from the outside in as if it's a disease, as if it's encountering something, a virus, for example, the immune system sees it as foreign. It jumps to alert, and then it starts seeking where those antigens may be.
And so a vaccine, a therapeutic vaccine versus a chickenpox, which is more prophylactic, right, you do it to prevent it, already, patients already have a tumor. We can sequence that tumor. We know what the features of that tumor are, and we could immunize the patient's immune system to put it on alert to find those antigens. But then, at that point, the tumor starts fighting back, and that's where you start seeing the fact that the tumor may be more powerful than that immune system, And that's when a PD-one or a CTLA-four may be really critical. And a CTLA-four, Dan has coined this statement, at least in my eyes, when he has said CTLA-four is the agent that allowed us to put cure and cancer in the same sentence.
And it's that agent that not only do we see the tail of the curve phenomenon for the statisticians in the audience, but we see those patients who do survive, they are alive for a long, long time, in many cases cured, and that's a durable response that CTLA-four could incite. So we know how powerful it is. We know that in certain contexts you need PD-one and CTLA-four, as well as others, and I'm going to go into that. The reason today you need PD-one in your pipeline is because you must have it for optimal combinations. We've seen that.
Whether it's standard of care agents, many different approaches, you need a PD-one. Cell therapy approach is another place where you're going to need a PD-one. If I try to run a study today and I need to get access to a commercially available PD-one, I'm paying for it full price, I'm getting it out of the market, or I've got to get a pharmaceutical company who has access to it for them to allow me to use it if I'm not accessing it in the market. And that's incredibly complex. Now, let's say I don't have it, and I get through all of those hurdles.
I test my products, and they work together in their optimal benefits with someone else's PD-one, and then I want to commercialize that product. I already have their fixed price baked into my combination price, which is not affordable for patients as we're seeing this financial toxicity. You must have your own CTLA-four and PD-one. They are the only IO agents that work, and you have to have them in your portfolio. We're one of two, three companies that have these agents within our pipeline, and we're the most advanced CTLA-four PD-one in the clinic right now and path to BLA.
And what I will say that Gaurav brought up a point about the importance of how could we actually extract even more value out of our PD-one, our lead molecules. And now we dip into what I believe to be the real beauty of Agenus and where this true inflection is going to happen. And that's in some of the discoveries that our scientists have made, a discovery that was made here in the genus published in Cancer Cell last June in which we have identified and made the discovery in which we can engineer a CTLA-four for a next generation approach that not only addresses the two main mechanisms of CTLA-four, but it also does something that no other CTLA-four available right now does, and that is it enhances the priming or the education time of when an antigen and an immune cell are talking. And when you get that superior education, you're going to work better. You're going to work much more efficiently.
And so if you increase that time, you can increase your effectiveness of your immune cells, the priming of your T cells, and the antitumor activity. The molecules in the clinic, it's going through dose escalation right now, and we'll be combining it with our own PD-one in a matter of months. So we're very excited about it.
And we'll have some answers by the end of the year. That's the most important
thing. It is about it's not X, it's DXPT. It's that change over time. I want to get a sense of your baby, your PD-one, and just get so that the audience can understand that a little bit. But I want to make sure that if we have anyone on the phone, did we have questions in the queue since I know it is getting a little late?
Or in the audience.
Questions in the audience or any questions that were in the queue from listeners?
As it stands there are no questions in the audio queue. As a reminder if you would like to ask a question it is star then one.
So tell me about your PD. You guys have this luxury of knowledge, and I think a lot of people in the audience may not understand it. So tell me about it. Tell me what the baby
It's a beautiful, Absolutely beautiful beautiful. It works, it works well. We have very advanced trials. So our PD-one is in a path, a BLA path trial, a registrational trial. We've already spoken with the FDA.
We may have additional interactions coming up soon. But that molecule itself, and we've presented data at major conferences over the past couple of years showing the pharmacology of the molecule, showing the clinical activity of the molecule. And what's most important to us is that the molecule works, that it's bringing the benefit to patients that we designed it to do and that we expect or hope from it. And what we are seeing now from the clinic in patients in a number of different tumor types, ovarian, cervical, sarcomas, etcetera, that the molecule is active, that we see and we presented data that over sixty percent of patients have disease control when they're on our PD-one. Some of those are responses, some of those are complete responses, but regardless, their disease is controlled, which means that when a patient goes to get that next scan, it's their disease is stable, it's not it's either getting better, it's not getting any worse, right?
So that is an incredible experience I could imagine from a patient. When you have that scan, which you have to do every six weeks, and you get the news that things look good. And so sixty eight percent on our PD-one monotherapy, we publicly disclosed these data at ESMO last year. And just under that for our combination CTLA-four and PD-one, those patients, the majority of patients treated have that experience, that disease control.
Is there any reason to suggest or think that your PD-one in combination with other therapies has specific advantages because they were developed together or uniquely?
There are a number of advantages that our PD-one, first that we have it and that it's working very well, and it's working at least as well as the commercially available agents. And that's the those are the data that we have seen to date. Additionally, the molecule in combination with other agents is active as well. It hasn't been designed specifically to partner with a specific product, but it's designed to function and address the mechanisms that we need to unleash the immune system and allow it to attack cancer. And maybe I'll ask you, Dan, if you want to say anything Yeah,
absolutely. So when you consider having anti P or anti CTLA-four in your portfolio, it's important that you recognize that they act at two different points in the immune response to cancer. CTLA-four, as Jen mentioned, is enabling the education and the priming of that T cell response to Early, That's early, very early
Correct. Okay.
Now when that T cell now is activated and it's ready to kill, they will encounter barriers. PD L1 happens to be one of those barriers. Our anti PD-one addresses that. And if I could add to Jen's comment, our therapies are not only performing in the clinic, but they're also showing responses in areas where you don't typically expect. This is very important because being able to bring therapy to patients
Tell me the areas. I should have introduced myself as the forward thinking guy because I'm always going to push a little bit ahead of where the science wants to support. Entertain me for
a second here on the goes back to, you know, the promise of AGenesis to bring therapies to a broader patient population, to position our therapies in areas where patients are underserved. And this is where we're we've, you know, positioned our pipeline, our PD-one and CTLA-four agents, and this is where we're seeing responses.
John, may I ask a very provocative question? I called you a provocateur, but you haven't earned that yet.
Not yet.
But let me ask a tough question and perhaps I can answer it. So if we are so good at this and uniquely positioned, And we've been around for twenty five years. Why don't we have a product in the market already? That's the question. Is that a reasonable question?
You know, it's very interesting because we didn't put any hash marks on here, you know? If you talk about the airplane business, this is extraordinary long, sixty seven years. If you talk about Pokemon Go, this is the course of weeks. So I think it's an interesting question. I'm gonna try to answer it after you because I have some ideas about it.
Okay. So my answer is very simple, and it's not an excuse or trying to rationalize the reality. We have to remember that the first twenty years of that twenty five year birth was comprised of a single modality that we tried to make it work in multiple different conditions, meaning we had an individualized cancer vaccine, we tried to develop it for one indication, and unfortunately it didn't work. This was renal cell carcinoma, and I don't want to bore you with the reasons why it didn't work, but it wasn't the fault of the agent, it was the fault of a lot of things. But it took us twenty years to have access to many other tools that are now known today as critically necessary in order for us to battle and combat cancer.
So we didn't have them. We got them in through acquisitions and internal discoveries and that period is only about five years. And we didn't even get started until the year after, so we're talking about four years.
Yeah.
And but in that four year period, what we have accomplished is short of a miracle. I mean, it is a remarkable feat what the company has accomplished. A pipeline that is unprecedented. And I don't take credit for it. It's my colleague that take full credit for it because they have been the discoverers of this broad and deep pipeline.
And John, maybe I'll just stay to add on to this. So you mentioned it in your opening remarks, Garo, but in the past three years essentially we filed more discoveries, brought more discoveries to the clinic than any of our large pharma competitors. 11 INDs were filed. Nine of those programs are in the clinic right now in monotherapy or in combinations with others in our own pipeline and with partnered programs. Gaurav may have mentioned that we, because of our discovery engine that we've amassed, so this belly of the curve here that you see here, and that constricted timeline of about four years, we have brought in, built, amassed the technology to go from an idea to developing a therapeutic approach, testing it pre clinically, manufacturing it at record speed five to six times industry standard, all in house.
So from that idea to that patient, and just faster than what I have seen any other company do, that's the belly of the curve. We're at the point right now where with nine of those programs in the clinic within our own pipeline and through partnered programs, we're going to see this trajectory, I think, enhance dramatically. But beyond that, others have seen the value of this pipeline, right? I mean, we concluded the largest deal in oncology in 2018 with Gilead on a preclinical asset. Really dramatic and exciting time and with an incredible collaborator.
We discovered a molecule that Merck is advancing in the clinic targeting ILT4 now disclosed. We have licensed our QS-twenty one adjuvant to GSK, and it is in the world's most effective vaccine, ninety seven percent effective, and over $2,000,000,000 in sales projections. Those efforts are now being realized here, but within such a short period of time, imagine with the opening remarks that you made about that trajectory what the future looks like, what the real possibility is for us here.
This is a really tough place to live. This is a difficult place. This is where conviction lives. This is where Elon Musk lives. This is where people who have a vision live.
And it's only empowered by an idea whose time has come. And it's that constellation of issues that are important and dramatic. It's lonely here. It's very, very difficult. I want to ask you
I'm trying to
come up with a tough question now. Fill in the blank. Pharma, big pharma, is my blank. I'm going to give you some options. Partner?
Demesis? Adversary? Competition? I find a unique relationship with pharma, big pharma, that is both interesting and problematic. Kind of tease that out a little bit.
I think it's an important concept.
I think you can say it's all of those things that you talked about, plus a freight train that will take an effort to stop. I mean, when I look at big pharma and I'll be provocative, of course there are exceptions, there are smart companies out there, but for the most part, I look at big pharma as an industry that would be defined as a sunset industry. And what that means is that they have created a trap for themselves, a trap of extremely high cost, a fixed cost structure that will be very difficult to shed, that's number one. And also a trap based on very high pricing of product. I mean, for example, look at some of the competition in PD-one or CTLA-four.
That price has been fixed by them. If they change that pricing from where it has been fixed, it would have detrimental consequences on their companies, on their shareholder value and everything else. Whereas we are starting from ground zero and our cost structure is low to start with, our cost of developing product is much lower than theirs plus our pricing flexibility and I'm not suggesting that we will go around cutting prices necessarily but what I'm suggesting is that we will price products and combinations of product responsibly. Responsibly in a way that is affordable by the system and is not designed to put us out of business because of exorbitant pricing of healthcare product countervail.
My sense is that you're intellectually and functionally flexible. Yes. And I'll use the George Washington Carver peanut analogy because I don't want to mention companies. But it seems to me the objective of George Washington Carver was to find as many possible ways I could use this peanut. And I find that certain compounds are being run through clinical trials to expand indication for the sake of growing revenue.
I think that's sort of antithetical to what I'm hearing here.
That's right. I mean, you hit it on the nail. It's exactly what they're doing right now. So it's very difficult to believe. In fact, in our discussions I made a comment about the fact that our discussions with potential partners and collaborators are at a very, very high pace right now.
And in our discussions with a major pharma executive, not a biotech but a major pharma executive who is in the immuno oncology business, he basically said we're ready to shut down our internal innovation because it doesn't exist. It doesn't exist.
Do we have some questions in the back? Saw some shuffling. If you don't ask a question I'm going to keep talking and you know how that goes. So okay, I want to wrap up my comments with something that I think is very interesting that I stumbled over just this week. And I was reading through some things.
And I saw a quote. And the quote said, and I looked it up and people have said it many, many times. I'm not even going to tell you who in particular said this. It said, If I stop learning, I die. Stop learning, I die.
And wow,
That's cancer in a way when you think about it. Beginning to understand the immunological profile of cancers, they're really smart. It's a smart disease. It tricks our immune system. So cancer is constantly learning.
And when we can stop it from learning, we can kill it. And to me, the next step to that is that's not cancer. That's egenics. That's what you're doing. You're constantly learning that you're not driven by convention.
You're not driven by profit motive to take RPD one and drive it across 20 indications. You're looking at doing the right thing but being very smart about it. So every time I come here, I learn something new. And I hope that education lasts for a very, very long time. You very much.
Thank you.
Thank you very much, John. First of all, John has taken an enormous amount of time and effort to learn about Agenus. So he didn't come here just as a guest but he came in having invested heavily in understanding our company, having met a substantial number of the innovators and the management at the company. So thank you very much for that. And I might add that I very much appreciate many of your patients.
It's been a long time. And, it's been a long time, but will, you know, it's frustrating at times and if you're invested in Agenus as a team member or as an investor, you wonder, you know, are we alone here in having been penalized, particularly in the last year or so, or even before? And the answer to that question is no, we are not alone, because we've had an immuno oncology sector that's comprised of approximately 30 plus companies in the $10,000,000,000 lower than $10,000,000,000 category. If you look at that category, the market value of the cumulative sector has shrunk in the last twelve months from approximately 52,000,000,000 to approximately 41,000,000,000. That's a 20% shrinkage.
And if you look at the individual players in that sector, there are only a handful whose market value has increased during that twelve month period. And it's us amongst the handful of players. Our market capitalization, I'm not talking about stock because there are all kinds of transactions that drive market capitalization, has increased by approximately 50%. And that's the table that shows it. For example, if you look at this right most column, which is the list of companies that are valued at less than 10,000,000,000, our market value has increased by 59% in the last twelve months, and this is the performance of most of the members of the sector.
So hopefully, as I say, the light is at the end of the tunnel, it's much more visible today than ever before because we've got a huge pipeline. And as we talked about, the pipeline is designed to have high impact effect on cancer patients, which means that, for example, if our next generation CTLA-four will do what we hope it to do, we will be able to decipher that data in 2,030 patients. I'm not suggesting that we'll necessarily be able to register it with twenty, thirty patient data, but if it is profoundly effective, we will know it in 20 to 30 patients. And that kind of information will be out in reasonable order. And that's only one of many products, as Jen mentioned, in our pipeline.
So thank you very much for your time and patience and we hope to see you here under much more pleasant circumstances next year. Thank